T-cells are the principal cells of the mammalian immunological system. They are produced in the thymus from stem cells of bone marrow. T-cells are responsible for maintaining tissue integrity and cell-mediated immunity. It is known that the in vivo mechanism of T-cell action comprises activation of surface receptor sites on T-cells: upon contact with foreign antigens such as invading bacteria or foreign cells, which causes the T-cells to transform into blast cells and to release mediator chemicals called lymphokines which induce various immunological responses including the production of interferon (IFN).
Further advances in the understanding of T-cell function and lymphokines have awaited in vitro culture of the cells. T-cells may be isolated from the spleen or intraperitoneal cavity of animals immunized with tumor cells, but until recently it has not been possible to establish and maintain these cells for prolonged periods of time.
An important development in the investigation of T-cells has been the discovery of T-cell growth factor (TCGF), subsequently designated interleukin 2 (IL-2), which permits the continuous culture and cloning of T-lymphocytes in vitro (Braciale, T. J., Andrew, M. E., and Braciale, V. T. J. Exp. Med., 153:910-923, 1981, Gillis, S., and Smith, K. A. Nature, 268:154-156, 1977, Rosenberg, S. A., Spiess, P. J., and Schwartz, S. J. Immuno., 121:1946-1950, 1978, Ruscetti, F. W., Morgan, D. A., and Gallo, R. C. J. Immunol., 199131-138, 1977, Von Boehmer, H., Hengartner, H., Nabholz, M., Lernhardt, W., Schreier, M. H., and Haas, W. Eur. J. Immmunol., 9:592-597, (1979)).
The addition of interleukin-2 (IL-2) to activated T-cell populations allows for their continuous expansion and their establishment as long-term cell lines. This availability of cultured T-cells allows the examination of the production and regulation of lymphokines in a simplified homogeneous system.
Interferons (IFN) are a heterogeneous group of proteins that prevent replication of viruses in a host cell and thus protect against viral infections. They mediate other biological activities as well. (Stewart, W. E. 1979. The Interferon System. Springer-Verlag, New York, N.Y., Farrar, W. L., H. M. Johnson, and J. J. Farrar. J. Immunol. 126:1120, (1981)). Interferons are classified by their antigenicity into three classes: IFN-.alpha., IFN-.beta. and IFN-.gamma. or immune IFN (Stewart, W. E., J. E. Blalock, D. C. Burke, C. Chang, J. K. Dunnick, E. Falcoff, R. M. Friedman, G. J. Galasso, W. K. Joklik, J. T. Vilcek, J. S. Younger, and K. C. Zoon, Interferon Nomenclature, Nature (London) 286:110, (1980)).
IFN-.gamma. has been produced in vitro from peripheral blood lymphocytes in humans and spleen cell cultures in mice. (Archer, D. L., B. G. Smith, J. T. Ulrich, and H. M. Johnson. Cell. Immunol. 48:420, (1979). However, in these complex systems, the regulation of IFN-.gamma. production and the various activities of this lymphokine have been difficult to define (Farrar, W. L., et al. Sopra, Dinh, P. N. I. Beladi, I. Rosztoczy, and M. Toth., J. Interferon Res. 1:23, (1980)). High levels of IFN-.alpha.,.beta. have been made available by the isolation and characterization of cell lines capable of producing these classes of IFN.
However, homogeneous T-cell clones which produce IFN-.gamma. and other lymphokines at significant levels are still being sought.